DNA vaccination is promising for a wide range of therapeutic and preventive indications but is yet to demonstrate clinical success in humans. Consensus in the field is that suboptimal potency and inefficiency of conventional delivery methods is a key hurdle. The use of in vivo electroporation (EP) provides multi-log increases in DNA uptake and expression in a variety of tissues. When used for DNA immunization, EP-mediated intramuscular (i.m.) or intradermal (i.d.) delivery of DNA vaccines significantly enhances the magnitude and consistency of immune response compared to conventional injection. The central challenge for the clinical implementation of this technology is the provision of devices capable of safe, effective, and reproducible delivery in a manner appropriate for clinical use. Due to its accessibility and the presence of a spectrum of antigen presenting cells in the skin, i.d. DNA immunization is of particular interest. When compared to other methods of DNA delivery to skin, EP is well positioned due to its delivery efficiency, high level antigen expression, robust dose capacity, and utility across cell types. Ichor has developed platform EP technology (TriGrid Delivery System-TDS) designed for safe, effective, and reproducible DNA delivery in the clinical setting. Based on its experience in the development of an EP device for i.m delivery (TDS-IM) that is currently in clinical studies for multiple indications, the company is well positioned to develop technology for i.d. delivery. Towards this end, Ichor initiated development of prototype devices for EP mediated i.d. DNA immunization (TDS-ID) with the objective of providing a simple, reproducible delivery device to support commercial vaccine development. Preliminary results demonstrate induction of potent immune responses in multiple species. Efforts are now focused on development of devices suitable for use in clinical trials. A central design issue yet to be addressed is the selection of an injection technology capable of achieving consistent i.d. DNA distribution when integrated with the EP device. In Phase I, performance of multiple candidate i.d. injection technologies will be characterized in an animal model of human skin (swine). The criteria for evaluation will include: 1) magnitude and consistency of i.d. delivery as assessed by reporter gene expression and 2) quantitative and qualitative analysis of the immune responses elicited against a model antigen. The proposed studies will provide the basis for finalizing device design as well as a valuable data set to facilitate partnering/collaboration. If the feasibility milestones for Phase I are achieved, Phase II will comprise development and testing of an integrated TDS-ID device suitable for use in human clinical trials. The overall objective of Phase II would be the submission of a device master file to the US FDA to provide the foundation to initiate clinical testing of TDS-ID administration of DNA vaccine candidates developed by Ichor or its partners. PUBLIC HEALTH RELEVANCE: The proposed project will evaluate the basic feasibility of a novel integrated device for electroporation mediated intradermal (i.d.) DNA vaccine delivery. By providing a simple method to achieve effective and consistent i.d. DNA vaccine delivery, the proposed device could facilitate DNA vaccines for indications including cancer, infectious disease and allergy. [unreadable] [unreadable] [unreadable]